AETIOLOGY,PATHOPHYSIOLOGY AND

DIAGNOSIS OF DENGUE INFECTION

DR LEE OI WAH
PEG. PERUBATAN UD54
Dengue Virus
Causes dengue and dengue hemorrhagic fever
Is an arbovirus
Transmitted by mosquitoes
Composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)


Dengue Viruses
Each serotype provides specific lifetime
immunity, and short-term cross-immunity
All serotypes can cause severe and fatal
disease
Genetic variation within serotypes
Some genetic variants within each serotype
appear to be more virulent or have greater
epidemic potential
4
1






















Circulating Dengue Virus Serotype : 1992-2007
0
10
20
30
40
50
60
70
80
90
100
DEN 1 DEN 2 DEN 3 DEN 4
DEN 1 3.7 0 4.8 14.7 48.7 63.5 44.4 28.2 9.3 5.4 29.8 46.9 73.4 58.6 33 30
DEN 2 8.6 4.1 9.5 29.5 48.7 33.4 51.9 69.2 58.1 39.2 23.8 20.6 7.4 8.4 36.4 53
DEN 3 83.7 93.1 84.1 54.6 2.6 2.1 3.7 2.7 32.6 50 33.3 27.8 14.6 17.1 19.3 11
DEN 4 4 2.8 1.6 1.2 0 0 0 0 0 5.4 13.1 4.7 4.6 1.2 4.5 6
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Serotype Surveilan Di Ng Perak 2002 - 2007
Year
No of
Samples
Type 1 Type 2 Type 3 Type 4
2002 113 0 1 1 2
2003 22 0 0 0 0
2004 8 0 1 0 0
2005 250 4 1 3 2
2006 160 4 0 4 1
2007 243 9 19 7 0
Total 796 17 22 15 5
DENGUE VECTORS
Aedes aegypti
Aedes albopictus
Larva
Pupa
1 - 2 Days
1 - 3 Days
6 - 8 Days
2 - 3 Days
Water
LIFE CYCLE OF THE AEDES
Adult
Eggs Hatch 1- 48 hrs
Complete cycle 9 10 days
DENGUE TRANSMISSION

Infected Person Susceptible
Person
Mosquito Bite
Infected
Mosquito
Infected Mosquito
Bites next person
Becomes Sick
Mosquito Bite
Infected
Mosquito
3 14 days later
Remains viremic
2 to 10 Days
8 12 DAYS
Manifestations of the dengue
syndrome
Asymptomatic
Undifferentiated
fever
No h'rage Unusual
hemorrhage
Dengue Fever
DHF I & II DSS
Dengue Hemorrhagic Fever
(plasma leakage)
Symptomatic
Dengue virus
Infection
Fever lasting 2-7 days, occasionally biphasic

Bleeding tendencies

Thrombocytopenia (100,000/mm3 or less)

Evidence of plasma leakage: Haemoconcentration (20%
above baseline)
A drop in haematocrit following fluid replacement
Pleural effusion, ascites (not obvious in early stage of
critical phase), circulatory disturbances.

Hypovolemic shock
Dengue Haemorrhagic Fever (WHO 1997)
Dengue Shock Syndrome (WHO 1997)

All the above 4 criteria for DHF, plus evidence of
circulatory failure:

rapid and weak pulse
narrow pulse pressure less than 20mmHg
or
hypotension for age
cold clammy skin and restlessness

WHO grading of DHF/DSS (WHO
1997)

Grade 1
In the presence of haemoconcentration, fever and symptoms, a positive TT
Grade 2
spontaneous bleeding in addition to the manifestation from Grade 2
Grade 3*
circulatory failure, pulse pressure less than 20 mmHg but systolic pressure
normal
Grade 4*
profound shock, hypotension or unrecordable blood pressure.

Simplification:
Grade 1 & 2: Non-shock DHF
Grade 3: COMPENSATED shock
Grade 4: DECOMPENSATED shock #
Dengue Case Classification
13 Dengue Perak 5/2010
PATHOPHYSIOLOGY OF DENGUE
INFECTION



Deferversence
24-48 hours

Recognition of onset of reabsorption
phase is also important because i.v fluid
regime needs to be progressively
reduced/ discontinued at this stage.
Thrombocytopenia

120
110
100
90
80
70
60
Blood pressure, pulse pressure, heart rate in hypovolemic shock
Time
LCS Lum
Compensated shock Decompensated shock
First sign of shock is tachycardia
Followed by increasing diastolic BP
Drop is systolic BP is relatively late event
PR
DIAGNOSIS OF DF OR DHF
Important points to evaluate:
History:
date of onset of fever/ illness
nausea, vomiting, abdominal pain, diarrhoea
bleeding tendency
change in mental state/seizure/dizziness
urine output (frequency, volume and time of last voiding)
other important relevant histories:
family or neighbourhood history of dengue
jungle trekking and swimming in waterfall (consider leptospirosis,
typhus, malaria)
travelling
recent unprotected sexual or drug use behaviour (consider acute
HIV seroconversion illness)
co-morbidities (consider sepsis in patients with diabetes mellitus)
Physical examination:

Assess mental state and GCS score
Assess haemodynamic status
Cold/ warm extremities
Capillary filling time (normal < 2 seconds);
Pulse rate and Pulse volume
Blood pressure and Pulse pressure
Look out for tachypnoea/ acidotic breathing/ pleural
effusion
Check for abdominal tenderness/ hepatomegaly/ ascites
Examine for bleeding manifestation
Tourniquet test (repeat if previously negative or if there
is no bleeding manifestation)
Investigations:

FBC & HCT
Renal and liver function tests
INR & APTT
Dengue serology
BFMP
Other relevent tests
After clinical assessment
1. Day.fever
2. Temp chart Febrile phase / Critical phase
Hours of defervescence
3. Alarm signals Yes/No
Abdominal pain and vomiting / Restlessness / Cold and
clammy extrimities / Altered conscious level / A sudden
change from fever to hypothermia
4. Bleeding tendency Yes/No
5. Evidence of plasma leakage Yes/No
Pleural effusion / Ascites
Hemodynamic instability - INCLUDING
TACHYCARDIA (PR>90)
Increase in HCT






Diagnosis :
Dengue Haemorrhagic Fever
D6 illness
Deferversence 12 hours
With right pleural effusion and ascites
Clinically no alarming signs / bleeding

(EXAMPLE)